Controlled Human Malaria Infection at the Walter Reed Army Institute of Research: The Past, Present, and Future From an Entomological Perspective.

Thirty years ago, the Entomology Branch at the Walter Reed Army Institute of Research (WRAIR) performed the first controlled human malaria infection, in which lab-reared mosquitoes were infected with lab-cultured malaria parasites and allowed to feed on human volunteers. The development of this model was a turning point for pre-erythrocytic malaria vaccine research and, through decades of refinement, has supported 30 years of efficacy testing of a suite of antimalarial vaccines and drugs. In this article, we present a historical overview of the research that enabled the first challenge to occur and the modifications made to the challenge over time, a summary of the 104 challenges performed by WRAIR from the first into 2015, and a prospective look at what the next generation of challenges might entail.